Remotely Controlled Surface Charge Modulation of Magnetoelectric Nanogenerators for Swift and Efficient Drug Delivery.

We have developed a highly efficient technique of magnetically controlled swift loading and release of doxorubicin (DOX) drug using a magnetoelectric nanogenerator (MENG). Core-shell nanostructured MENG with a magnetostrictive core and piezoelectric shell act as field-responsive nanocarriers and possess the capability of field-triggered drug release in a cancerous environment. MENGs generate a surface electric dipole when subjected to a magnetic field due to the strain-mediated magnetoelectric effect. The capability of directional magnetic field-assisted modulation of the surface electrical dipole of MENG provides a mechanism to create/break ionic bonds with DOX molecules, which facilitates efficient drug attachment and on-demand swift detachment of the drug at a targeted site. The magnetic field-assisted drug-loading mechanism was minutely analyzed using spectrophotometry and Raman spectroscopy. The detailed time-dependent analysis of controlled drug release by the MENG under unidirectional and rotating magnetic field excitation was conducted using field-emission scanning electron microscopy, energy-dispersive X-ray, and atomic force microscopic measurements. In vitro, experiments validate the cytocompatibility and magnetically assisted on-demand and swift DOX drug delivery by the MENG near MCF-7 breast cancer cells, which results in a significant enhancement of cancer cell killing efficiency. A state-of-the-art experiment was performed to visualize the nanoscale magnetoelectric effect of MENG using off-axis electron holography under Lorentz conditions.

3D microscaffolds with triple-marker sensitive nanoprobes for studying fatty liver disease in vitro.

Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition that encompasses a wide range of liver diseases that progresses from simple hepatic steatosis to the life-threatening state of cirrhosis. However, due to the heterogeneity of this disease, comprehensive analysis of several physicochemical and biological factors that drive its progression is necessary. Therefore, an in vitro platform is required that would enable real-time monitoring of these changes to better understand the progression of these diseases. The earliest stage of NAFLD, i.e. hepatic steatosis, is characterised by triglyceride accumulation in the form of lipid vacuoles in the cytosol of hepatocytes. This fatty acid accumulation is usually accompanied by hepatic inflammation, leading to tissue acidification and dysregulated expression of certain proteases such as matrix metalloproteinases (MMPs). Taking cues from the biological parameters of the disease, we report here a 3D in vitro GelMA/alginate microscaffold platform encapsulating a triple-marker (pH, MMP-3 and MMP-9) sensitive fluorescent nanoprobe for monitoring, and hence, distinguishing the fatty liver disease (hepatic steatosis) from healthy livers on the basis of pH change and MMP expression. The nanoprobe consists of a carbon nanoparticle (CNP) core, which exhibits intrinsic pH-dependent fluorescence properties, decorated either with an MMP-3 (NpMMP3) or MMP-9 (NpMMP9) sensitive peptide substrate. These peptide substrates are flanked with a fluorophore-quencher pair that separates on enzymatic cleavage, resulting in fluorescence emission. The cocktail of these nanoprobes generated multiple fluorescence signals corresponding to slightly acidic pH (blue) and overexpression of MMP-3 (green) and MMP-9 (red) enzymes in a 3D in vitro fatty liver model, whereas no/negligible fluorescence signals were observed in a healthy liver model. Moreover, this platform enabled us to mimic fatty liver disease in a more realistic manner. Therefore, this 3D in vitro platform encapsulating triple-marker sensitive fluorescent nanoprobes would facilitate the monitoring of the changes in pH and MMP expression, thereby enabling us to distinguish a healthy liver from a diseased liver and to study liver disease stages on the basis of these markers.

Remote supratentorial intraparenchymal bleed after posterior fossa surgery: A rare occurrence.

Background: Intraparenchymal hemorrhage at the operative site is one of the major complications of brain surgery. It is unusual to occur at a site remote from the operative site, but when it happens, it may cause significant morbidity and mortality. Case Description: We report the case of a 27-year-old male who presented with complaints of paresthesias over the left side of his face and decreased hearing from the left ear for two years. His radiology was suggestive of a large left cerebellopontine angle epidermoid cyst. The patient underwent left retro mastoid suboccipital craniotomy and near-total excision of the epidermoid cyst. The immediate postoperative non-contrast computed tomography scan of the brain was suggestive of no hematoma at the operated site but a remote left parafalcine frontoparietal intraparenchymal bleed, which was managed conservatively. At two months follow-up, he had no neuro deficits, and magnetic resonance imaging of the brain was suggestive of near-total excision of the epidermoid cyst with resolving left parafalcine frontoparietal bleed. Conclusion: We report this case due to the unique case observation of an intracranial bleed at a remote site rather than at the operated site.

Dual-Sensitive Fluorescent Nanoprobes for Simultaneously Monitoring In Situ Changes in pH and Matrix Metalloproteinase Expression in Stiffness-Tunable Three-Dimensional In Vitro Scaffolds.

A tumor microenvironment often presents altered physicochemical characteristics of the extracellular matrix (ECM) including changes in matrix composition, stiffness, protein expression, pH, temperature, or the presence of certain stromal and immune cells. Of these, overexpression of matrix metalloproteinases (MMPs) and extracellular acidosis are the two major hallmarks of cancer that can be exploited for tumor detection. The change in matrix stiffness and the release of certain cytokines (TNF-α) in the tumor microenvironment play major roles in inducing MMP-9 expression in cancerous cells. This study highlights the role of mechanical cues in upregulating MMP-9 expression in cancerous cells using stiffness-tunable matrix compositions and dual-sensitive fluorescent nanoprobes. Ionically cross-linked 3D alginate/gelatin (AG) scaffolds with three stiffnesses were chosen to reflect the ECM stiffnesses corresponding to healthy and pathological tissues. Moreover, a dual-sensitive nanoprobe, an MMP-sensitive peptide conjugated to carbon nanoparticles with intrinsic pH fluorescence properties, was utilized for in situ monitoring of the two cancer hallmarks in the 3D scaffolds. This platform was further utilized for designing a 3D core-shell platform for spatially mapping tumor margins and for visualizing TNF-α-induced MMP-9 expression in cancerous cells.

Oxonium ion scanning mass spectrometry for large-scale plasma glycoproteomics.

Protein glycosylation, a complex and heterogeneous post-translational modification that is frequently dysregulated in disease, has been difficult to analyse at scale. Here we report a data-independent acquisition technique for the large-scale mass-spectrometric quantification of glycopeptides in plasma samples. The technique, which we named 'OxoScan-MS', identifies oxonium ions as glycopeptide fragments and exploits a sliding-quadrupole dimension to generate comprehensive and untargeted oxonium ion maps of precursor masses assigned to fragment ions from non-enriched plasma samples. By applying OxoScan-MS to quantify 1,002 glycopeptide features in the plasma glycoproteomes from patients with COVID-19 and healthy controls, we found that severe COVID-19 induces differential glycosylation in IgA, haptoglobin, transferrin and other disease-relevant plasma glycoproteins. OxoScan-MS may allow for the quantitative mapping of glycoproteomes at the scale of hundreds to thousands of samples.

A Miniaturized, Low-Frequency Magnetoelectric Wireless Power Transfer System for Powering Biomedical Implants.

This work experimentally demonstrates the operation of a miniaturized magnetoelectric (ME) wireless power transfer (WPT) system by incorporating a ME transducer and a suitable interface power management circuit (PMC) for potentially powering implantable medical devices (IMD) wirelessly. A ME heterostructure is micromachined to obtain desired device dimensions of 3.5 × 5 mm 2 and to restrict the operating frequency at a clinically approved frequency of 50 kHz. The proposed work also aims to address the trade-off between the device miniaturization, power attenuation and limiting the specific absorption rate (SAR) in the human tissue. By limiting the operating frequency to 50 kHz, the SAR is reduced to less than 1 µW/kg. The fabricated device is characterized with low-intensity AC magnetic field up to 40 µT without using any DC bias, resulting in 0.4 V output voltage and 6.6 µW power across 8 k Ω load. Alignment misorientation between the Tx and Rx is studied for in-plane and out-of-plane angular rotations to confirm the device's reliability against angular misalignment. By eliminating the bulky biasing magnets, the proposed device achieves a significant size reduction compared to the previously reported works. In addition, a self-powered interface PMC is incorporated with the ME system. The PMC generates 3.5 V regulated DC voltage from the input AC voltage range 0.7 V to 3.3 V. The PMC is fabricated on a 2-layered PCB and the over all ME WPT system consumes 12 × 12 mm 2 area. The overall PMC has intrinsic current consumption less than 550 nA with peak power conversion efficiency higher than 85 %. The in vitro cytotoxicity analysis in the human hepatic cell line WRL-68 confirmed the biocompatibility of the Parylene-C encapsulated ME device for up to 7 days, suggesting its potential use in implantable electronic devices for biomedical and clinical applications.

The Upstate New York Surgical Quality Improvement Opioid Reduction Project.

Over 5 million Americans currently abuse prescription opioids. Patients' first exposure to opioids is often after surgery. Few opioid guidelines account for the challenges to health care institutions that serve wide catchment areas. We standardized postoperative opioid prescribing recommendations amongst surgical providers at our institutions and analyzed postoperative prescribing habits. The Upstate New York Surgical Quality Improvement (UNYSQI) collaborative met with surgical champions from 16 hospitals to standardize opioid prescribing for 21 surgical procedures. The guidelines were distributed to all surgical care providers at participating institutions. 581,465 pills were dispensed for 12,672 surgeries (average of 45.9 pills per procedure) before implementation. Post-implementation, 1,097,849 pills were dispensed for 28,772 surgeries (average of 38.2 pills per surgery) with over 222,000 fewer pills being prescribed. Our project suggests opioid prescribing guidelines for institutions that serve diverse communities.

Impact and Consequences of Recipient Gastroduodenal Artery Ligation Before Hepatic Artery Anastomosis During Orthotopic Liver Transplantation.

OBJECTIVES: The recipient's gastroduodenal artery is often ligated before the hepatic artery anastomosis during orthotopic liver transplant, to gain either mobility or length of recipient's hepatic artery, potentially protecting the anastomosis by preventing "steal syndrome." In this study, our aim was to evaluate the consequences of gastroduodenal artery ligation and its effect on prevention of hepatic artery thrombosis. MATERIALS AND METHODS: We retrospectively analyzed deceased-donor orthotopic liver transplant procedures (n = 210) performed at a single center between January 2016 and July 2021 to compare outcomes between recipients with (group 1) and recipients without (group 2) gastroduodenal artery ligation. Group 1 included 78 patients (37%), in which the recipient's common hepatic artery was used for arterial anastomosis; group 2 included 132 patients (63%), in which the right hepatic artery orthe proper hepatic artery was used for arterial anastomosis. Occurrences of hepatic artery thrombosis, postoperative hyperamylasemia, nausea and vomiting, and delayed feeding were compared between the groups. RESULTS: There was no incidence of hepatic artery thrombosis reported in either group. In group 1, 31 patients (39.7%) were reported to have postoperative hyperamylasemia, ranging from 200 to 4700 U/L accompanied by delayed feeding, whereas, in group 2, only 16 of 132 patients (12%) had postoperative hyperamylasemia, ranging from 200 to 1400 U/L (P < .01). CONCLUSIONS: Ligation of recipient's gastroduodenal artery is not associated with decreased risk of hepatic artery thrombosis compared with nonligation. However, the procedure does have consequences in the form of possible postoperative hyperamylasemia, leading to delayed feeding probably due to decreased oral tolerance.

Exploring the relationship between air quality index and lung cancer mortality in India: predictive modeling and impact assessment.

The Air Quality Index (AQI) in India is steadily deteriorating, leading to a rise in the mortality rate due to Lung Cancer. This decline in air quality can be attributed to various factors such as PM 2.5, PM 10, and Ozone (O3). To establish a relationship between AQI and Lung Cancer, several predictive models including Linear Regression, KNN, Decision Tree, ANN, Random Forest Regression, and XGBoost Regression were employed to estimate pollutant levels and Air Quality Index in India. The models relied on publicly available state-wise Air Pollution Dataset. Among all the models, the XGBoost Regression displayed the highest accuracy, with pollutant level estimations reaching an accuracy range of 81% to 98% during training and testing. The second-highest accuracy range was achieved by Random Forest. The paper also explores the impact of increasing pollution levels on the rising mortality rate among lung cancer patients in India.

Advancements in Intraoperative Near-Infrared Fluorescence Imaging for Accurate Tumor Resection: A Promising Technique for Improved Surgical Outcomes and Patient Survival.

Clear surgical margins for solid tumor resection are essential for preventing cancer recurrence and improving overall patient survival. Complete resection of tumors is often limited by a surgeon's ability to accurately locate malignant tissues and differentiate them from healthy tissue. Therefore, techniques or imaging modalities are required that would ease the identification and resection of tumors by real-time intraoperative visualization of tumors. Although conventional imaging techniques such as positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), or radiography play an essential role in preoperative diagnostics, these cannot be utilized in intraoperative tumor detection due to their large size, high cost, long imaging time, and lack of cancer specificity. The inception of several imaging techniques has paved the way to intraoperative tumor margin detection with a high degree of sensitivity and specificity. Particularly, molecular imaging using near-infrared fluorescence (NIRF) based nanoprobes provides superior imaging quality due to high signal-to-noise ratio, deep penetration to tissues, and low autofluorescence, enabling accurate tumor resection and improved survival rates. In this review, we discuss the recent developments in imaging technologies, specifically focusing on NIRF nanoprobes that aid in highly specific intraoperative surgeries with real-time recognition of tumor margins.

Critical analysis of the reporting quality of case reports focusing on dental traumatology using the Preferred Reporting Items for Case reports in Endodontics 2020 checklist: A baseline evaluation prior to checklist publication.

BACKGROUND/AIMS: The Preferred Reporting Items for Case Reports in Endodontics (PRICE) 2020 guidelines were published to help authors produce high-quality case reports. The aim of this study was to use the PRICE 2020 guidelines to appraise a sample of 50 case reports related to dental traumatology that were published before the guidelines were available in order to assess various parameters influencing the reporting quality. METHODS: Fifty case reports published between 2015 and 2019 and related to dental traumatology were randomly selected from the PubMed database. Reports were assessed by two independent evaluators using the PRICE checklist. Each item received a score of "1" if the manuscript met all pertinent criteria, "0" if it was not reported, and "0.5" if it was reported insufficiently. "Not Applicable" (NA) was assigned to items that were irrelevant to a specific report. The estimated total PRICE score for each case report was computed by adding all the scores, with a maximum score of 47 minus any "NA" scores. Descriptive and Inferential statistics (Student's t-test and ANOVA) were used for analysis. RESULTS: The percentage of case reports that fully met each applicable criteria ranged from 0% to 100%. The percentage of case reports partially satisfying each applicable criterion varied from 0% to 88%. There was a significant difference in scores for case reports published in journals with an impact factor compared with those without (p = .042). No significant difference was observed between the mean scores that compared the period of publication. There was no significant difference between journals that followed the CARE guidelines and those that did not. CONCLUSION: Several items within the PRICE 2020 guidelines were either not reported or only partially reported in case reports related to dental traumatology prior to the checklist publication. It is recommended that authors follow the PRICE 2020 guidelines to improve the overall quality of their case reports.

Spontaneously established syntrophic yeast communities improve bioproduction.

Nutritional codependence (syntrophy) has underexplored potential to improve biotechnological processes by using cooperating cell types. So far, design of yeast syntrophic communities has required extensive genetic manipulation, as the co-inoculation of most eukaryotic microbial auxotrophs does not result in cooperative growth. Here we employ high-throughput phenotypic screening to systematically test pairwise combinations of auxotrophic Saccharomyces cerevisiae deletion mutants. Although most coculture pairs do not enter syntrophic growth, we identify 49 pairs that spontaneously form syntrophic, synergistic communities. We characterized the stability and growth dynamics of nine cocultures and demonstrated that a pair of tryptophan auxotrophs grow by exchanging a pathway intermediate rather than end products. We then introduced a malonic semialdehyde biosynthesis pathway split between different pairs of auxotrophs, which resulted in increased production. Our results report the spontaneous formation of stable syntrophy in S. cerevisiae auxotrophs and illustrate the biotechnological potential of dividing labor in a cooperating intraspecies community.

Potential treatments of COVID-19: Drug repurposing and therapeutic interventions.

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is caused when Spike-protein (S-protein) present on the surface of SARS-CoV-2 interacts with human cell surface receptor, Angiotensin-converting enzyme 2 (ACE2). This binding facilitates SARS-CoV-2 genome entry into the human cells, which in turn causes infection. Since the beginning of the pandemic, many different therapies have been developed to combat COVID-19, including treatment and prevention. This review is focused on the currently adapted and certain other potential therapies for COVID-19 treatment, which include drug repurposing, vaccines and drug-free therapies. The efficacy of various treatment options is constantly being tested through clinical trials and in vivo studies before they are made medically available to the public.